MITRAL VALVE REGURGITATION INDUCES STRUCTURAL CHANGES

二尖瓣反流引起结构变化

• 批准号: 2399123
• 负责人: RICHARD P COCHRAN
• 金额: $ 35.72万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-15 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2399123
• 关键词: biomechanics; clinical research; collagen; computer assisted patient care; computer simulation; disease /disorder model; elastin; heart function; histopathology; human subject; immunocytochemistry; light microscopy; mechanical stress; mitral valve; mitral valve insufficiency; morphology; mucopolysaccharides; myocardial ischemia /hypoxia; procollagen; protein biosynthesis; scars; sheep; structural biology; tissue /cell preparation

DESCRIPTION: (Adapted from investigator's abstract) The broad long term objectives of this research are to use a unique 3-D computer model to improve the timing and type of treatment offered to patients with mitral valve regurgitation, and to assess whether there is a role for earlier valve repair in selected etiologies. As the valve is affected by disease, the functional anatomy is often altered, the valve becomes regurgitant, and the normal distribution of mechanical stresses is disrupted. It is the central hypothesis of this application that mitral valve regurgitation, itself, induces structural changes and alters mechanical function. The clinical implication of this hypothesis is that the longer a valve is regurgitant, the more disrupted will be the tissue and the less likely that a surgical repair would be successful. The applicants proposed to test several aspects of this theory and will delineate the mechanisms that contribute to this process, in a three part approach. In Part One, they proposed to assess whether regurgitation induces structural change. Experimental sheep models will be used in which mitral regurgitation is created either by papillary muscle ischemia, or by disruption of the chordae tendineae. After 4, 8, or 16 weeks of regurgitation, the valves will be evaluated for the amount of and the distribution of collagen, as well as changes in elastin and glycosaminoglycans (GAGs). This will answer: 1) Is there an increase in collagen synthesis and/or a change in collagen types in experimentally created mitral regurgitation? 2) Is there a difference in collagen synthesis, collagen types or collagen distribution due to the mechanism of regurgitation? and 3) Is there a concurrent increase in the other structural components of the valve (elastin and glycosaminoglycans (GAGs)) due to regurgitation. In Part Two, the applicants proposed to assess whether the structural change is accompanied by changes in the mechanical properties of mitral valve tissue. The sheep model will be repeated, and in addition human valves will be obtained from explanted hearts from transplant recipients. The biaxial mechanical properties of both will be determined, as well as the collagen orientation to answer: 4) How do the microstructural changes alter the mechanical properties of the valve tissue? 5) Do the pathologic changes seen in human valves parallel either of the experimental models? Finally, in Part Three, the applicants proposed to determine the effect of structural and mechanical property changes on valve function. A three dimensional finite element model will be used which will incorporate the data obtained in Parts One and Two, to answer: (6) Do the microstructural and mechanical property changes significantly alter valve function as tested in a finite element computer model of the mitral valve? 7) Should clinical management of mitral valve disease be altered?

描述：(改编自调查人员摘要)广泛的长期 本研究的目标是使用一种独特的3-D计算机模型来 改善二尖瓣病变患者的治疗时机和类型 瓣膜返流，并评估早期瓣膜是否起作用 修复选定的病因。由于瓣膜受到疾病的影响， 功能解剖经常改变，瓣膜变得反流， 机械应力的正态分布被打乱。它是中央 这一应用的假说是二尖瓣返流本身， 导致结构变化并改变机械功能。临床部 这一假设的含义是瓣膜返流的时间越长， 组织受到的破坏越大，手术越不可能 修复将是成功的。申请者提出了几个方面的测试 并将描绘出促成这一理论的机制 流程，采用三部分方法。在第一部分，他们建议评估 反流是否会导致结构变化。实验用绵羊模型 将用于二尖瓣关闭不全是由乳头状肌 肌肉缺血，或肌腱索断裂。在4、8或 16周的返流，将评估瓣膜的量 以及胶原的分布，以及弹性蛋白和 糖胺聚糖(GAG)。这个问题的答案是：1)…… 实验性的胶原合成和/或胶原类型的改变 造成二尖瓣返流？2)胶原蛋白有区别吗？ 合成，胶原类型或胶原分布，由于机制 反胃？3)另一项指标是否同时增加 瓣膜的结构成分(弹性蛋白和糖胺多聚糖(GAG)) 由于反胃。在第二部分，申请者建议评估 结构变化是否伴随着机械结构的变化 二尖瓣组织的特性。绵羊模型将重复，并在 额外的人体瓣膜将从移植后的移植心脏中获得 收件人。这两种材料的双轴机械性能将被确定， 以及胶原蛋白的取向回答：4)怎么做的 微结构变化会改变瓣膜组织的机械性能吗？ 5)人体瓣膜的病理变化是否平行于 实验模型？最后，在第三部分中，申请者建议 确定结构和机械性能变化对阀门的影响 功能。将使用三维有限元模型，它将 结合在第一部分和第二部分中获得的数据，回答：(6)做 瓣膜的显微组织和力学性能发生显著变化 在二尖瓣的有限元计算机模型中测试的功能？ 7)二尖瓣病变的临床处理应该改变吗？